The present invention relates to a vaccine against the pathogenic protozoan Neospora which vaccine is useful in the prevention of clinical disease and abortion in mammals. The vaccine of the invention comprises an homogenate prepared from cells of a species of Neospora.
Neosporosis in mammals is caused by infection with a pathogenic strain of the protozoan parasite Neospora, and has been recognized as a major cause of abortion, neonatal death, congenital infection, and encephalitic disease. Dubey and Lindsay, 1996, Vet. Parasitol. 67:1-59; Dubey and Lindsay, 1993, Parasitol. Today 9:452-458. Neospora caninum infects dogs and congenitally infects pups, often leading to paralysis. Tachyzoites of N. caninum have been isolated from naturally infected pups. Lindsay and Dubey, 1989, J. Parasitol. 75:163-165. Infection with Neospora is also a major cause of abortion in dairy cattle. Cases of neosporosis have also been reported in goats, sheep and horses.
Although N. caninum is superficially similar to the pathogen Toxoplasma gondii, N. caninum and T. gondii are distinguishable from each other both antigenically and ultrastructurally. Dubey and Lindsay, 1993, above. In addition, Neospora-like protozoan parasites isolated from the brains of aborted bovine fetuses and continuously cultured in vitro were shown to be antigenically and ultrastructurally distinct from both T. gondii and Hammondia hammondi, and most similar to N. caninum. Conrad et al., 1993, Parasitology 106:239-249. Furthermore, analysis of nuclear small subunit ribosomal RNA genes revealed no nucleotide differences between Neospora strains isolated from cattle and dogs, but showed consistent differences when compared to T. gondii, thus confirming the distinction between pathogens. Marsh et al., 1995, J. Parasitol. 81:530-535.
The etiologic role of a bovine isolate of Neospora in bovine abortion and congenital disease has been confirmed. Barr et al. 1994, J. Vet. Diag. Invest. 6:207-215. A rodent model of central nervous system neosporosis has been developed using inbred BALB/c mice infected with N. caninum. Lindsay et al, 1995, J. Parasitol. 81:313-315. In addition, models to study transplacental transmission of N. caninum in pregnant outbred and inbred mice have been described by Cole et al., 1995, J. Parasitol. 81:730-732, and by Long et al., 1996, J. Parasitol. 82:608-611, respectively. Furthermore, an experimental N. caninum pygmy goat model closely resembling naturally acquired Neospora-induced cattle abortion has been developed. Lindsay etal., 1995, Am. J. Vet. Res. 56:1176-1180.
WO 9525541 discloses a biologically pure culture of bovine Neospora, methods of detecting anti-Neospora antibodies and Neospora-specific nucleic acids, and a composition containing a bovine Neospora antigen and carrier for use as a vaccine.
An effective vaccine against neosporosis comprising an homogenate prepared from cells of Neospora has not previously been disclosed.
In a first aspect, the present invention provides an homogenate prepared from cells of Neospora, which homogenate is capable of inducing a protective response against neosporosis in a mammal.
In a second aspect, the present invention provides a vaccine to protect a mammal against neosporosis, comprising an immunologically effective amount of an homogenate prepared from cells of Neospora, which homogenate is capable of inducing a protective response against neosporosis in a mammal, and a veterinarily acceptable carrier. The vaccine of the present invention may further comprise one or more additional immunomodulatory components including, e.g., an adjuvant or cytokine.
In a third aspect, the present invention provides a method for preparing a vaccine that protects a mammal against neosporosis, comprising homogenizing cells of Neospora to form an homogenate capable of inducing a protective response against neosporosis in a mammal. and combining an immunologically effective amount of the homogenate with a veterinarily acceptable carrier in a form suitable for administration to the mammal.
In a fourth aspect, the present invention provides a method for protecting a mammal against neosporosis, comprising administering to the mammal a vaccine comprising an immunologically effective amount of an homogenate prepared from cells of Neospora, which homogenate is capable of inducing a protective response against neosporosis in a mammal, and a veterinarily acceptable carrier. The vaccine of the present invention may be administered to any mammalian species susceptible to infection and disease caused by Neospora, including but not limited to dogs, cows, goats, sheep and horses.
In a fifth aspect, the present invention provides a combination vaccine for protecting a mammal against neosporosis and, optionally, one or more other diseases or pathological conditions that can afflict the mammal, which combination vaccine comprises an immunologically effective amount of a first composition comprising an homogenate prepared from cells of Neospora, which homogenate is capable of inducing a protective response against neosporosis in a mammal; an immunologically effective amount of a second composition capable of inducing a protective response against a disease or pathological condition that can afflict the mammal; and a veterinarily acceptable carrier.
The second composition of the combination vaccine is selected based on its ability to induce a protective response against either neosporosis or another disease or pathological condition that can afflict members of the mammalian species, as known in the art. The combination vaccine of the present invention may further comprise one or more additional immunomodulatory components including, e.g., an adjuvant or cytokine, among others.
In a sixth aspect, the present invention provides a kit for vaccinating a mammal against neosporosis, comprising a first container having an immunologically effective amount of an homogenate prepared from cells of Neospora, which homogenate is capable of inducing a protective response against neosporosis in a mammal, and a second container having a veterinarily acceptable carrier or diluent suitable for mixing with the contents of the first container.
In a seventh aspect, the present invention provides antibodies specific to one or more antigenic components present in an homogenate prepared from cells of Neospora.